Helicobacter Pylori Related Gastric Cancer Screening and Cost-Effectiveness Analysis: A Hospital-Based Cross-Sectional Study (SIGES)

Figures & data

Table 1. Baselines between cancer-free controls and gastric cancer cases.

Baselines	Controls, n (%)	Gastric cancer, n (%)	p value
Total	15,599	163
Age (yrs)			<0.001^a
<20	367 (2.3)	0
20–39	4,410 (28.3)	11 (6.7)
40–59	7,969 (51.1)	66 (40.5)
≥60	2,853 (18.3)	86 (52.8)
Sex			<0.001^b
Male	7,237 (46.4)	100 (61.4)
Female	8,362 (53.6)	63 (38.6)
Ethnicity			0.119^b
Han	15,358 (98.5)	158 (96.9)
Tibetan, Yi, others	241 (1.5)	5 (3.1)
Setting	(4:1)	(2:1)	0.002^b
Training	12,204 (78.2)	111 (68.1)
Validation	3,395 (21.8)	52 (31.9)

a, Wilcoxon test; b, Chi-square test.

Table 2. Hp prevalence between cancer-free controls and gastric cancer cases.

	Controls Hp +, n (%)	Gastric cancers Hp +, n (%)	aOR	p value
Total	6,419 (41.2)	91 (55.8)	1.79 (1.31–2.46)	<0.001
Subsets
Age
20–39 yrs	1,773 (40.2)	5 (45.5)	1.27 (0.39–4.15)	0.699
40–59 yrs	3,386 (42.5)	41 (62.1)	2.21 (1.34–3.64)	0.002
≥60yrs	1,141 (40.0)	45 (52.3)	1.60 (1.04–2.47)	0.033
Sex
Male	2,984 (41.2)	58 (58.0)	1.98 (1.32–2.96)	0.001
Female	3,435 (41.1)	33 (52.4)	1.55 (0.94–2.55)	0.086
Ethnicity
Han	6,277 (40.9)	87 (55.1)	1.78 (1.30–2.45)	<0.001
Tibetan, Yi, others	142 (58.9)	4 (80.0)*	1.89 (0.19–18.97)	0.588

* A trend of higher Hp prevalence in ethnic minority, but without significance.

Figure 1. ROCs of UBT alone and UBT-based model.

Table 3. AUC values of UBT predicting gastric cancer in training setting.

Category	AUC	95% CI	SE	p value
UBT alone	0.60	0.55–0.65	0.027	Ref
Model^a	0.78	0.74–0.82	0.021	<0.001
Subsets^b
Age (years)
20–39	0.65	0.43–0.87	0.112	Ref
40–59	0.67	0.59–0.75	0.040	0.861
≥60	0.64	0.56–0.71	0.040	0.925
Sex
Male	0.79	0.75–0.84	0.023	Ref
Female	0.75	0.67–0.83	0.039	0.362

Abbreviations: AUC: area under the curve; CI: confidence interval; Ref: reference; SE: standard error; UBT: urea breath test.

^aThe model included four variables, i.e., dpm value of UBT, age (years), gender, and ethnicity.

^bThe AUCs among the subsets were calculated using the model above.

Table 4. Diagnostic performance of the UBT-based index ^a generated from UBT for predicting gastric cancer.

Setting and cutoff	TP	FP	FN	TN	SEN	SPE
	N	N	N	N	% (95% CI)	% (95% CI)
Training setting
Optimal cutoff ^a	89	4,646	22	7,558	80.2 (71.5–87.1)	61.9 (61.1–62.8)
SPE at 80%	66	2,438	45	9,766	59.5 (49.7–68.7)	–
SPE at 90%	49	1,219	62	10,985	44.1 (34.7–53.9)	–
SEN at 80%	89	4,646	22	7,558	–	61.9 (61.1–62.8)
SEN at 90%	100	7,304	11	4,900	–	40.2 (39.3–41.0)
Validation setting
Optimal cutoff ^b	40	1,371	12	2,024	76.9 (63.2–87.5)	59.6 (57.9–61.3)

Abbreviations: CI: confidence interval; FN: false negative; FP: false positive; SEN: sensitivity; SPE: specificity; TN: true negative; TP: true positive; UBT: urea breath test.

^aIndex = 0.000432× dpm (value) + 0.0702× age (yrs) – 0.5756× sex (female =1, male = 0) + 1.5833× ethnicity (Tibetan, others =1, Han =0).

^bThe optimal cutoff was >2.864 for positivity, which was settled by the maximal Youden index in training setting.

Figure 2. Cost-effectiveness analysis on protocol candidates of Hp-GCS.

Table 5. Subpopulation strategy for endoscopic screening.

Sex	Age	Hp infection	Controls	Cancer	RR (95% CI)	NNS
Male	<40 yrs	UBT (–)	1,404	1	Ref	15,762
		UBT (1+∼2+)	862	1	1.63 (0.10–26.00)	9,682
		UBT (3+∼4+)	81	0*	1.73 (0.003–1,148.55)	9,087
	40–59 yrs	UBT (–)	2,047	15	9.81 (1.35–77.29)	1,607
		UBT (1+∼2+)	1,369	26	25.13 (3.56–192.71)	627
		UBT (3+∼4+)	133	3	29.74 (3.25–295.93)	530
	≥60 yrs	UBT (–)	802	26	43.78 (6.00–324.53)	360
		UBT (1+∼2+)	496	23	61.79 (8.43–459.90)	255
		UBT (3+∼4+)	43	5	145.23 (17.43–1,228.73)	109
Female	<40 yrs	UBT (–)	1,481	5	4.35 (0.55–40.42)	3,620
		UBT (1+∼2+)	684	3	5.65 (0.64–58.88)	2,789
		UBT (3+∼4+)	265	1	4.87 (0.33–84.19)	3,240
	40–59 yrs	UBT (–)	2,536	10	4.78 (0.71–43.07)	3,296
		UBT (1+∼2+)	1,466	8	6.61 (0.95–60.89)	2,385
		UBT (3+∼4+)	418	4	11.54 (1.49–118.83)	1,366
	≥60yrs	UBT (–)	910	15	20.63 (3.01–172.19)	764
		UBT (1+∼2+)	478	11	28.62 (4.09–244.18)	551
		UBT (3+∼4+)	124	6	58.73 (7.87–534.55)	268

Abbreviations: CI: confidence interval; Hp: Helicobacter pylori; NNS: number needed to screen; Ref: reference; RR: relative risk; UBT: urea breath test.

* A value 0.5 was assigned for null event.

Table 6. Cost-effectiveness analysis of protocol candidates for Hp-GCS.

Protocol	Detail	Cost ($)	Cases	DR	CER	Δcost ($)	ΔEffect	ICER
P1	Any age without UBT	1,300,990	163	100%	7,981.54	604,836	36	16,801.00
P2	Any age, but UBT (1 ∼ 4+)	782,520	91	55.8%	8,599.12
P3	Age ≥40 yrs and UBT (1 ∼ 4+)	551,462	86	52.8%	6,412.35
P4	Age ≥40 yrs and UBT (3 ∼ 4+)	231,456	18	11.0%	12,858.66
P5	Age 40-59 yrs and UBT (1 ∼ 4+), or age ≥60 yrs without UBT	696,154	127	77.9%	5,481.53	Ref	Ref
P6	Any age and UBT (3 ∼ 4+)	334,577	19	11.7%	17,609.32
P7	Age ≥40 yrs without UBT	905,790	152	93.3%	5,959.15	209,636	25	8,385.50
P8	Age <40 yrs and UBT (1 ∼ 4+), or age ≥40 yrs without UBT	1,136,848	157	96.3%	7,241.07	440,694	30	14,689.80
P9	Age <40 yrs and UBT (3 ∼ 4+), or age ≥40 yrs without UBT	1,008,912	153	93.9%	6,594.19	312,757	26	12,029.10

Abbreviations: CER: cost-effectiveness ratio; DR: detection rate; Hp-GCS: Helicobacter pylori related gastric cancer screening; ICER: incremental cost-effectiveness ratio; Ref: reference; UBT: urea breath test; yrs: years.